How forgiving is Isentress?

[Cliff]

Hi,

I was wondering how to guesstimate Isentress forgiving properties with regards to dosage?  Taken twice daily.

I know it's a function of half life, dosing, and molecular stuff!  Just a guesstimate of when it drops below theraputic levels in the blood after dosing.

Thank you

[mecch]

Just asked my current hiv doc this question.  Since I take it on a very flexible schedule but always 2x a day.  He said:  I can take the two pills one time a day if that is a way to reduce the possibility that I will miss the second dose. I said I don't miss the second.  He said, one time is OK because I've been undetectable for several years.  He said, its not the best of the drugs for sticking around, and so its better to stick to 2 different times, but he said my irregular schedule for those two times didn't matter much. 
Not very specific but thats the content of the conversation. Also he said that there is a "new" isentress formulation coming along eventually that is 1x a day. 

[emeraldize]

Also he said that there is a "new" isentress formulation coming along eventually that is 1x a day.

Really? What has he read that causes him to say that? The study done showed once daily dosing to be inferior. Or, does he have some other source of information?  http://www.aidsmap.com/page/1684212/

[newt]

After a few days, Isentress is forgiving enough 2 x day not to worry about a few hours* over on a dose. This is because after 2-3 days of taking it the drug reaches a steady concentration in your body and basically all you are doing is keeping it topped up.  1 x day a sub-therapeutic concentration may be reached in less than 24 hours, because you are topping up once only and even in the same person the decline in concentration can vary from day to day.

Also, I'd be sharp on not missing more than one dose. Isentress has a long half life and is therefore subject to the same problem as efavirenz after several missed doses, namely hanging around at low levels and encouraging resistance. Except efavirenz offers a bigger buffer here (days perhaps). Isentress is a take it or lose it drug.

Hope this helps

- matt

* someone will now ask what 'a few hours' means

[mecch]

Really? What has he read that causes his to say that? The study done showed once daily dosing to be inferior. Or, does he have some other source of information?  http://www.aidsmap.com/page/1684212/

You have misread me or I was not clear?  My doc said there is new formulation in the pipeline, coming along, not on the market yet, of Isentress that will be 1x a day.  But maybe I misunderstood him.  Well I'll ask him again in 3 weeks when I need to call him about something.

[Cliff]

Thanks all.  Very helpful.

[emeraldize]

You have misread me or I was not clear?  My doc said there is new formulation in the pipeline, coming along, not on the market yet, of Isentress that will be 1x a day.  But maybe I misunderstood him.  Well I'll ask him again in 3 weeks when I need to call him about something.

Hi Mecch,
Nope. I understood what you wrote. I wanted to know what he's read or heard that caused him to report this to you given the results of the once-daily dosing of Isentress being found to be inferior. I'm quite curious...whenever you get a chance I'll be interested.
Thanks.
Em

[Ann]

My doc said there is new formulation in the pipeline, coming along, not on the market yet, of Isentress that will be 1x a day.  But maybe I misunderstood him.

It might be that you misunderstood him - he might have been talking about Dolutegravir which is in the same class as Isentress, but isn't new formulation of Isentress.

This drug is in the pipeline and most people will be able to take it once a day (unless there are Isentress resistance issues, then it's twice daily). Trials are currently in Phase III. My doctor is very excited about this new med.

Cliff, I just realised this is in the Living forum. I'll move it to Treatments.

[eric48]

Hi,

I have never been able to get an answer from my Doc (nor any other) concerning my own combo about how forgiving it can be...

There is no really convincing 'data' since pharmaco-kinetics do not explain everything.

In order to provide a better 'efficiency' profiling of each drug, Shen and Siliciano have introduced a compounded IIP index that combines drug efficiency, clearance, residence, etc.
IIP = Instantaneous inhibitory potential

all the way down (at page 14) of the following article:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743464/

schematic A gives a pretty clear picture of how drugs compare to each other over time.

If you rate a flat line as 'rather forgiving' and a 'sharp slope' as not forgiving at all, you pretty much rank the meds as they are usually ranked by the word of mouth.

On this schematic EFV has a high IIP that remains flat
NVP (which I take) does not: it a a bit less forgving... The slope for Raltegravir (Insentress) is intermediate, but with a pretty low (also sufficient) IIP

This is for individual drugs. Coformulation and extended release can provide additionnal forgiveness. On top of that there are 3 drugs in your combo...

As an exemple, Indinavir has the steepest slope and indeed the aidsmeds drug profile says:
Crixivan can be taken either three times a day or twice a day

I think the above mentioned diagram is consistent with the comments/posts here above, and provides a very 'graphic' understanding of what you may be told about this matter.

Hope this helps

Eric

[laxdude01]

I started on the combo Isentress/Truvada in 3/2010 a little over a year after I tested HIV+.  My initial numbers were 15k/VL, 1030CD4.  I took my doctor's recommendation to start when I did, given after 15 month my CD4 dropped to 710... yes, above the CDC 500 threshold to begin meds... but her concern was with any possible organ damage research has been discovering affects those with even smaller amounts of virus in the body.

I had the common fears-- what about side effects?  what if I miss a dose?  I've never been good with consistently taking meds.  She told me this combo had low reports of side effects, but strict adherence is a must.. skipped or even late doses could be problematic.

I've surprised myself in being able to keep up pretty well with taking them regularly on time... I can't say I've been perfect.  Three times (that I can remember) I missed a dose... probably a dozen times I've been 4-8 hours late.  The times I've been late, I'd push ahead the next dose a few hours so as not to miss it, but still create enough space between them.

I've been very fortunate to have been seeing great results.  My VL went undetectable the next time labs were checked after beginning the meds.  As for the CD4 levels, they have done nothing but increase in that time... from when they were at 710 initially going on meds, to 1630 at my last blood draw two months ago.

My doctor had told me at the time I started treatment that this combo has had the greatest results when it comes to those who have gone through a long list of combos and never seeing their VL get to undetectable, prevalent amongst those with long-term diagnoses.  Apparently this drug has done that with a substantial number of them. 

So that's my story, for what it's worth.  I have no complaints whatsoever with the status quo and hope they continue to work for me for as long as possible.  Adherence is the best thing to keep that happening, so I'll continue to do my best to religiously take them on time.

[Common_ground]

Hi,

I have never been able to get an answer from my Doc (nor any other) concerning my own combo about how forgiving it can be...

There is no really convincing 'data' since pharmaco-kinetics do not explain everything.

In order to provide a better 'efficiency' profiling of each drug, Shen and Siliciano have introduced a compounded IIP index that combines drug efficiency, clearance, residence, etc.
IIP = Instantaneous inhibitory potential

all the way down (at page 14) of the following article:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743464/

schematic A gives a pretty clear picture of how drugs compare to each other over time.

If you rate a flat line as 'rather forgiving' and a 'sharp slope' as not forgiving at all, you pretty much rank the meds as they are usually ranked by the word of mouth.

On this schematic EFV has a high IIP that remains flat
NVP (which I take) does not: it a a bit less forgving... The slope for Raltegravir (Insentress) is intermediate, but with a pretty low (also sufficient) IIP

This is for individual drugs. Coformulation and extended release can provide additionnal forgiveness. On top of that there are 3 drugs in your combo...

As an exemple, Indinavir has the steepest slope and indeed the aidsmeds drug profile says:
Crixivan can be taken either three times a day or twice a day

I think the above mentioned diagram is consistent with the comments/posts here above, and provides a very 'graphic' understanding of what you may be told about this matter.

Hope this helps

Eric

Interesting reading, especially figure 4A.
Thanks for sharing.